Endo-Repro Drugs and Enzymes

Question 1

What is the mechanism of Bisphosphonates and what can they be used to treat?

Answer 1

Bisphosphonates promote osteoclast apoptosis and inhibit osteoclast activity of breaking down hydroxyapatite. This drug can be used to lower serum Ca++ levels and treat osteoporosis by lowering the rate of demineralization.

Question 2

What diuretic may lead to hypercalcemia if used excessively?

Answer 2

Thiazide diuretics = increase Ca++ reabsorption at DCT in the nephron

Question 3

What exogenous hormone can be used in conjunction with Bisphosphonates to lower plasma Ca++?

Answer 3

Calcitonin can be used to deposit Ca++ into mineralized bone.

Question 4

What is the function of Clomiphene?

Answer 4

Clomiphene is an Estrogen receptor antagonist that lowers the E2-dependent negative feedback on gonadotropin secretion. This enables ovulation and is a treatment method for infertility as well as PCOS.

Question 5

What is the function of Letrozole?

Answer 5

Letrozole is an aromatase inhibitor that blocks the action of CYP19 of converting testosterone into E2. This would be great to lower the high levels of estrogen seen in Estrogen-resistant Syndrome.

Question 6

What is the mechanism and effect of Eplerenone?

Answer 6

Eplerenone is an Aldosterone antagonist that works by blocking the mineralocorticoid receptor. It can be used to prevent Na+ reabsorption and promote pressure natriuresis in patients with HTN.

Question 7

Define the effect and clinical significance of prednisone and dexamethisone.

Answer 7

Prednisone and Dexamethisone are cortisol agonists. They can be used to decrease ACTH levels by negative feedback and or stimulate Cortisol’s effects.

Question 8

Describe what the GnRH stimulation test can be used for. What effect does this have on pre-pubescent children?

Answer 8

GnRH stimulates the secretion of LH > FSH from the anterior pituitary. Exogenous GnRH should have no effect on pre-pubescent children since the gonadotropes have not been activated yet. This can be used to test for central precocious puberty, if LH secretion is noted in a young child with such signs/symptoms.

Question 9

What is the function of Bromocriptine or Cabergoline?

Answer 9

Dopamine agonist which opposes the effects of Prolactin and GH. These are possible treatments for amenorrhea for women with issues of menstrual cycles and infertility. It can also stop milk production and be used as a treatment for acromegaly (GH excess)

Question 10

Describe the function and location of 5’-deiodinase.

Answer 10

Converts T4 prehormone into active T3. This is found in follicular cells of the thyroid gland.

Question 11

Describe the function and location of 5-deiodinase.

Answer 11

Converts T4 into inactive reverse-T3 hormone; found in the thyroid gland.

Question 12

Describe the function and location of CYP11A enzyme.

Answer 12

Catalyzes progestin production and converts Cholesterol into Pregnenolone (P5). This is the rate-limiting step for steroidogenesis. Can be found in the adrenal cortex and preovulatory granulosa cells.

Question 13

Describe the function and location of CYP17 enzyme.

Answer 13

Catalyzes production of Androgens. This converts P5 into DHEA and 17-alphahydroxy-P4 into A-dione. This is expressed in the zona reticularis and preovulatory theca cells.

Question 14

Describe the function and location of 17-alpha-hydroxylase.

Answer 14

This converts P4 into Aldosterone and Cortisol. A deficiency in this enzyme (found in the adrenal cortex) presents with high testosterone and DHEA-S. A patient with this deficiency can have acne and high amount of body hair.

Question 15

Describe the function and location of CYP19 enzyme.

Answer 15

Aromatizes androgens into estrogens. More specifically: A-dione into E1, Testosterone into E2 and DHEA into E3. This is found in pre-ovulating Granulosa cells.

Question 16

Describe the function and location of 17-beta-HSD.

Answer 16

Converts A-dione into Testosterone; found in GC of the follicles within ovaries.

Question 17

Describe the function and location of 5-alpha-reductase.

Answer 17

Converts Testosterone into DHT; found in tissues outside the testes such as the prostate gland which relies on the latter for growth.

Question 18

Describe the function and location of 3-beta-HSD.

Answer 18

Converts P5 into P4 and DHEA into A-dione. This can be found in Theca cells of the follicles within ovaries and the Zona reticularis.

Question 19

Describe the function and location of Type 1 11-HSD.

Answer 19

This converts inactive Cortisone into active Cortisol hormone. It is expressed in the pituitary gland, liver, bones and gonads. Damage to the pituitary gland, for example, can reduce cortisol levels.

Question 20

Describe the function and location of Type 2 11-HSD.

Answer 20

Expressed in the kidney and aldosterone-targeting tissue. Converts Cortisol into INACTIVE Cortisone. Renal failure lowers Type 2 11-HSD which can result in elevated levels of Cortisol.

Question 21

Describe the function and location of CYP27B1.

Answer 21

Aka “1-alpha-hydroxylase” converts Vitamin D into Calcitriol which increases Calcium absorption in the gut and phosphate reabsorption in the PCT.

Question 22

Describe the function and location of PNMT enzyme.

Answer 22

Converts Norepinephrine into Epinephrine in the catecholamine biosynthesis pathway within the adrenal medulla. Can be up-regulated by elevated Cortisol levels.

Question 23

Describe the function and location of Tyrosine Hydroxylase.

Answer 23

Converts Tyrosine into DOPA as the first step in catecholamine biosynthesis. Expressed in the adrenal medulla.

Question 24

What is the function and location of CYP21.

Answer 24

Converts 17-alpha-hydroxy-P4 into 21-deoxycortisol. This enzyme is found in the zona reticularis.

Question 25

What is the significance of 17-alpha-hydroxyprogesterone? What might abnormal levels of this steroid indicate?

Answer 25

This is the immediate precursor to A-dione via CYP17 enzyme. High levels of this indicates a 17-alpha-hydroxylase deficiency, which is associated with Congenital Adrenal Hyperplasia (CAH).